Early PSA progression in abiraterone/enzalutamide-treated patients with metastatic castration-resistant prostate cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16530-e16530
Author(s):  
Fernando López-Campos ◽  
Alfonso Gomez-Iturriaga ◽  
Casilda Llacer Perez ◽  
Ivan Henriquez ◽  
Paula Peleteiro ◽  
...  

e16530 Background: Changes in PSA are widely used as a biomarker for the monitoring of treatment outcome in Metastatic Castration-Resistant Prostate Cancer (mCRPC) in the clinical real-world setting. Early PSA changes (before 12 weeks) are not considered in the definition of PSA Progression (PSAProg) due to the potential for spurious “flare” reactions. We aimed to evaluate the significance of an early PSA increase in Abiraterone/Enzalutamide (Abi/Enz)-treated mCRPC patients (pts). Methods: We retrospectively evaluated Abi/Enz-treated mCRPC pts from 11 hospitals between 2011-2018. Early PSAProg was defined as a 25% increase in PSA from baseline at 4 (PSAProg4) or 8 (PSAProg8) weeks after treatment initiation. PSA progression at 12 weeks (PSAProg12) was confirmed by a second reading. Uni- and multivariable (MV) Cox regression models were conducted to explore the association of PSAProg and overall (OS) and radiographic progression-free (rPFS) survival. Sensitivity (Se), specificity (Sp) and predictive values (PPV, NPV) for the association of early PSAProg with PSAProg12 were calculated. Results: We analyzed 581 mCRPC pts; median follow-up: 19.1 months. 96 (17.1%); 105 (21.6%) and 85 (16.9%) pts had PSAprog at 4, 8 and 12 wks. PSAProg4 and PSAProg8 were significantly associated with confirmed PSAProg12. 55.3% of pts with PSAProg4 and 66.7% of pts with PSAProg8 had a confirmed PSAProg12. Only 9% of pts with no PSA prog at 4 wks and 4.1% of pts with no PSAProg8 had a confirmed PSAProg12. PSAProg4 had Se: 56.6%, Sp: 90.5%, PPV: 55.2%, NPV: 91% for the detection of PSAProg12. PSAProg8 had Se: 81.9%, Sp: 91.2%, PPV: 66.7%, NPV: 95.9% for the detection of PSAProg12. PSAprog at 4, 8 and 12 wks was significantly associated with OS and rPFS in uni- and MV Cox models (Table). Conclusions: Early PSAProg after Abi/Enz is significantly associated with both confirmed PSA Prog at 12 wks and outcome, and may help identify pts not benefitting from Abi/Enz before clinical or radiographic progression. Prospective validation studies are needed. [Table: see text]

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5024-5024
Author(s):  
Fernando López-Campos ◽  
David Lorente ◽  
Casilda Llacer Perez ◽  
Miguel Ramirez-Backhaus ◽  
Paula Peleteiro ◽  
...  

5024 Background: PSA value is widely used for the monitoring of treatment outcome in mCRPC in the clinical real-world setting. Early PSA changes are not considered in the definition of PSAProg due to the potential for spurious “flare” reactions. We aimed to evaluate the significance of an early PSA increase in mCRPC patients (pts) treated with enzalutamide or abiraterone (Enz/Abi). Methods: We retrospectively evaluated Enz/Abi-treated mCRPC pts from 11 hospitals between 2011-2020. Early PSAProg was defined as a 25% increase in PSA from baseline at 4 (PSAProg4) or 8 (PSAProg8) weeks after treatment initiation. PSA progression at 12 weeks (PSAProg12) was confirmed by a second reading. Uni- and multivariable (MV) Cox regression models were conducted to explore the association of PSAProg and overall survival (OS) in chemotherapy naïve patients treated with Abi or Enz. Interaction tests were conducted to explore differences in the impact of PSA progression on OS in Abi or Enz-treated pts. Results: We analyzed 511 chemotherapy-naïve mCRPC pts treated with Abi (N=391; 76.5%) or Enz (N=120; 23.5%). Median follow-up: 30.2 months. OS was longer in Enz-treated pts (38.1 vs 29m; HR 1.4; p=0.027). 59 (15.1%), 70 (17.9%) and 48 (12.3%) of Abi-treated and 9 (7.5%), 11 (9.2%) and 10 (8.3%) of Enz-treated pts experienced PSAProg4, PSAProg8 and PSAProg12, respectively, although differences were not statistically significant. PSAProg was associated with worse OS at all 3 timepoints only in Abi-treated pts. In Enz-treated pts, PSAProg4 had a large impact on OS, not observed in PSAProg8 or PSAProg12. We observed no significant interaction between agent (Enz/Abi) and PSA progression (Table). Conclusions: PSA progression at 4 weeks after Enz/Abi is significantly associated with shorter OS and may help identify pts not benefitting from Abi/Enz before clinical or radiographic progression. PSA pattern progression and its association with OS might differ depending on the drug used (Enz/Abi). Prospective validation studies are needed.[Table: see text]


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 242-242
Author(s):  
Wataru Fukuokaya ◽  
Takahiro Kimura ◽  
Fumihiko Urabe ◽  
Shoji Kimura ◽  
Kojiro Tashiro ◽  
...  

242 Background: In the present guidelines for the management of metastatic castration-resistant prostate cancer (CRPC), it is unclear who benefits from androgen receptor axis-targeted agents (ARATs) or docetaxel as a first-line treatment. Methods: We conducted a single-institutional retrospective study to explore treatment-specific biomarkers for treatment response of metastatic CRPC. A cohort of 211 patients with metastatic CRPC treated with either ARAT (abiraterone acetate or enzalutamide) or docetaxel as a first-line treatment was evaluated. In addition to well-established biomarkers such as hemoglobin, neutrophil-to-lymphocyte ratio, alkaline phosphatase, and lactate dehydrogenase, we also assessed red cell distribution width, platelet count, and mean platelet volume (MPV). Laboratory measures were assessed within 1 month before starting treatment. Prostate-specific antigen progression-free survival (PSA-PFS) and radiographic progression-free survival (RPFS) were evaluated. Multivariable Cox regression models were used to assess the association between biomarkers and the risk of events. We also studied the statistical interaction between biomarkers and clinical outcomes. Results: Of all blood-based biomarkers, multivariable Cox regression models identified pre-treatment MPV (≤9.0 fL) as an independent prognostic factor of both PSA progression (hazard ratio [HR]: 2.62, 95% confidence interval [CI]: 1.25-5.48, P = 0.011) and radiographic progression (HR: 4.46, 95% CI: 1.79-11.1, P = 0.001). In addition, these models showed a lower risk of PSA progression (HR: 0.38, 95% CI: 0.15-0.96, P = 0.041) and radiographic progression (HR: 0.16, 95% CI: 0.05-0.50, P = 0.002) with docetaxel compared with ARAT when pre-treatment MPV was small. Conclusions: The present study identified MPV as a significant treatment-specific prognostic factor of PSA progression and radiographic progression in patients with metastatic CRPC treated with a first-line treatment. Furthermore, our results suggested that small MPV was associated with superior survival benefit on docetaxel over ARAT.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15195-e15195
Author(s):  
Carsten Henning Ohlmann ◽  
Michael Stöckle ◽  
David A. Pfister ◽  
Axel Heidenreich ◽  
Axel S. Merseburger ◽  
...  

e15195 Background: Abiraterone acetate (AA) plus prednisone (P) has demonstrated an improved survival of patients with castration-resistant prostate cancer (CRPC) compared to placebo plus P in a large phase III trial. In Germany, patients were able to receive AA within a compassionate-use program (CUP). Here, we report the first results of the program. Methods: Patients were eligible for the CUP if they progressed on or after at least one cytotoxic chemotherapy regimens. For CUP entry, patients were considered to have disease progression if they had radiographic evidence of disease progression in soft tissue or bone with or without PSA-progression and ongoing androgen deprivation. Patients received AA 1000mg daily plus prednisone 5mg BID until progression of disease or unacceptable toxicity. Results: Between 02-05/2011, 398 patients were registered for the CUP in Germany. Data from 191/350 (47.9%) of the patients treated at 10 different sites were available for evaluation of efficacy. Median age was 70.72yrs (52.35-87.61) and patients received a median of 1 (1-4) chemotherapy lines prior to CUP entry. Median PSA at baseline was 220.5 ng/ml (0.47-4245); 168 (88%) of patients presented with bone metastasis. With regard to efficacy, 64/191 (33.5%) of the patients showed an unconfirmed PSA-response ≥50%. At a median follow-up of 5.3 months, 51/191 (26.7%) patients had died, resulting in a median PSA-progression free and overall survival of 8.3 and 10.61 months, respectively. In a subset of patients (71/191, 37.2%) data regarding objective response was available with 25/71 (35.2%) achieving an objective response. Data from 114 pts. revealed fatigue (20.3%), hot flushes (15.8%), edema (10.6%), elevated liver enzymes (8.0%) and asthenia (7.9%) being the most frequent toxicities (any grade). Conclusions: Treatment of CRPC patients with AA outside controlled clinical trials leads to considerable PSA- and objective response rates with a favourable toxicity profile, comparable to the results from COU-AA-301 registration trial. Due to the short median follow-up, conclusions regarding PSA-progression free and overall survival may not be drawn.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5018-5018
Author(s):  
Anis Hamid ◽  
Himisha Beltran ◽  
Atish Dipankar Choudhury ◽  
Christopher Sweeney

5018 Background: Predictive genomic biomarkers in mCRPC remain elusive. Prior studies suggest that tumor suppressor (TS) loss is prognostic, and may result in less benefit from NHT, but no impact on D efficacy. We assessed genomic predictors of differential benefit of androgen receptor-targeted therapy and chemotherapy for mCRPC. Methods: Patients with mCRPC and targeted exome sequencing of biopsies obtained after metastatic diagnosis were identified (n=109). Patients with pure small cell histology (n=6) were excluded. Time from NHT or D start to clinical/radiographic progression (time to treatment failure, TTTF) was estimated by Kaplan-Meier method, with censoring at next therapy or last follow-up for non-progressors. Results: 80.1% of patients had bone and/or lymph node-only metastases at mCRPC diagnosis. In total, 87/103 (84.5%) and 61/103 (59.2%) received NHT and D for mCRPC, respectively. Median overall survival was 4.5 years from first mCRPC. The frequency and predictive association of selected recurrently-altered genes are detailed in the table. PTEN alterations (alts) were associated with worse TTTF on NHT, but not D, and a similar trend was observed with BRCA2. Biallelic RB1 loss was strongly predictive, conferring significantly shorter TTTF on both NHT and D. A score based on presence of tumor PTEN alt (1) and/or biallelic RB1 alt (1) was predictive of TTTF on NHT (median TTTF of score 0 vs 1 vs 2: 14.7 vs 12 vs 3.8 months; log rank p=0.003). Conclusions: The presence of single or compound PTEN and RB1 alts predict poorer outcomes with NHT for mCRPC. Chemotherapy may be a preferred therapeutic strategy for this patient population. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5049-5049
Author(s):  
Bram De Laere ◽  
Peter Van Oyen ◽  
Christophe Ghysel ◽  
Piet Ost ◽  
Wim Demey ◽  
...  

5049 Background: A heterogeneous landscape of patients with metastatic castration-resistant prostate cancer (mCRPC) exists in current clinical practice. We investigated the prognostic value of CTC enumeration and dynamics, in the context of second-line endocrine therapies (i.e. abiraterone or enzalutamide). Methods: In a prospective, multicentre study blood samples were collected from patients with mCRPC at baseline (n = 147) and follow-up (n = 95/147(64.6%)). At baseline, patients were stratified in favourable ( < 5 CTCs/7.5mL) and unfavourable (≥5 CTCs/7.5mL) groups, whereas at follow-up, in those demonstrating a stable, in- or decreasing CTC count. PFS and OS were compared between groups. PSA changes at 10-12 weeks were evaluable in 83 patients. Results: Patients with ≥5 CTCs/7.5 mL (n = 59) at baseline had a shorter PFS (3.9 vs. 11.3 months, p< 0.0001) and OS (9.34 months vs. not reached, p< 0.0001). Patients demonstrating increasing CTCs (n = 21) on therapy had a shorter PFS (4.03 vs. 10.36 vs. 13.08 months, p < 0.0001) and OS (11.2 months vs. not reached, p < 0.0001), compared to patients with decreasing (n = 41) and stable (n = 33) CTCs, respectively. Multivariate Cox regression showed that the number of CTCs (HR (95%CI): 1.0054 (1.0006–1.010), p= 0.0260) and an increasing follow-up CTC count (HR (95%CI): 2.8987 (1.2856–6.536), p= 0.0103) were independent predictors of PFS. CTC increase was the sole independent predictor for OS (HR (95%CI): 7.3512 (1.7953–30.101), p= 0.0055). At 10-12 weeks, a PSA response of ≥30% and ≥50% was achieved in 46/83 (55.4%) and 33/83 (39.8%) patients, respectively, which was statistically different between chemo-naive or -pretreated patients (≥30%: p= 0.0395), patients with increasing, stable or decreasing CTC counts (≥30%: p= 0.0019; ≥50%: p= 0.0032), and patients with increasing or stable/decreasing CTC counts (≥30%: p= 0.0006; ≥50%: p= 0.0014). Conclusions: CTC levels are associated with PFS and OS in mCRPC patients, starting a new line of endocrine therapy. Follow-up CTC enumeration is associated with PSA response and its dynamics is an independent predictor of PFS and OS, thereby demonstrating the pharmacodynamic properties of CTCs.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 178-178 ◽  
Author(s):  
A. Oliver Sartor ◽  
Daniel Heinrich ◽  
Neil Mariados ◽  
María José Méndez-Vidal ◽  
Daniel Keizman ◽  
...  

178 Background: Radium-223 (Ra-223) treatment (tx) is indicated for patients (pts) with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases (mets) (6 × 55 kBq/kg IV injections [inj]; 1 inj q4wk). Early results of an international, open-label, phase 1/2 study (NCT01934790) showed that re-treating pts with Ra-223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from a 2-year follow-up. Methods: Pts with CRPC and bone mets who completed 6 initial Ra-223 inj with no disease progression in bone and later progressed were eligible for Ra-223 re-tx (6 additional Ra-223 inj), provided that hematologic parameters were adequate. No concomitant cytotoxic agents were allowed; other concomitant agents (eg, abiraterone, enzalutamide) were allowed at investigator discretion. The primary objective was safety. Exploratory objectives were time to radiographic bone progression, radiographic progression-free survival (rPFS), overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE-free survival, all calculated from re-tx start. Pts will be followed for safety up to 7 years after last Ra-223 dose; an active 2-year follow-up evaluated exploratory objectives. Safety results from the active follow-up period and updated efficacy are reported. Results: 44 pts were re-treated with Ra-223; 29 (66%) completed all 6 inj (median number inj = 6). 34 (77%) of 44 pts entered active follow-up, during which no new safety concerns were noted. One new primary malignancy was reported (basal cell carcinoma). There were no serious drug-related adverse events. 19 (43%) of 44 pts had an rPFS event (radiographic progression or death); median rPFS was 9.9 months. Only 5 (11%) of 44 pts had radiographic bone progression; median time to radiographic bone progression was not reached. Median OS was 24.4 months. Median time to first SSE and SSE-free survival were 16.7 and 12.8 months, respectively. Conclusions: Re-treating with Ra-223 was well tolerated in this select pt population, led to minimal hematologic toxicity, and provided continued disease control in bone at 2-year follow-up. Clinical trial information: NCT01934790.


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 313-313
Author(s):  
Jinge Zhao

313 Background: AKR1C3 is a multifunctional enzyme playing a significant role in androgen synthesis and metabolism. Previous studies have proved that the activation of AKR1C3 was associated with resistance to abiraterone through increasing the intracrine androgen synthesis. However, clinical validation is still lacking as to the prognostic value of AKR1C3 in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone. Methods: Data of 117 patients with mCRPC between 2016-2018 in our center were retrospectively analyzed. AKR1C3 was detected by the immunohistochemical staining from the 12-core prostate biopsy. Kaplan-Meier curves and COX regression were used to analyze the association between AKR1C3 and the treatment outcomes of abiraterone. The endpoints of this study were PSA progression-free survival (PSA-PFS) and radiograph progression-free survival (rPFS). Results: In total, AKR1V3 was detected in 40/117 (34.2%) cases. The positive AKR1C3 was significantly associated with shorter PSA-PFS for mCRPC patients treated with abiraterone (median PSA-PFS: 6.2 Mo vs. 11.1 Mo, p < 0.001). Those with positive AKR1C3 were also accompanied with obviously poorer rPFS compared to those with negative AKR1C3 staining, despite that the difference was not statistically significant (median rPFS: 11.1 Mo vs. 21.8 Mo, p = 0.250). Multivariate COX regression indicated that, AKR1C3 was an independent prognosticator of rapid PSA progression for the abiraterone treatment (HR,95%CI: 2.612, 1.54-4.44, p < 0.001). Conclusions: This is the first study verifying the adverse prognostic significance of AKR1C3 for mCRPC patients receiving abiraterone treatment. Our results suggested that, AKR1C3 was closely related to early treatment failure of abiraterone, and thus, was worthwhile to be routinely described in pathological report.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Aseem Samar ◽  
Srikant Tiwari ◽  
Sundaram Subramanian ◽  
Nisarg Joshi ◽  
Jaykumar Sejpal ◽  
...  

Purpose. To evaluate the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS, DoceAqualip) in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods. In this multicenter, retrospective study, we analyzed the medical charts of mCRPC patients, who were treated with NDLS administered as 2-weekly (50 mg/m2) or 3-weekly regimens (75 mg/m2). The study endpoints were prostate-specific antigen (PSA) response (>50% PSA decline from baseline), PSA progression (PSA increase from baseline beyond 12 weeks: ≥25% and ≥2 ng/mL), median PSA decline, and time-to-treatment failure (TTF). Overall survival (OS) and safety were also evaluated. Results. Data of 24 patients with mCRPC were analyzed in this study. NDLS was administered as a 2-weekly regimen in 37.5% (9/24; all first-line) patients and as a 3-weekly regimen in 62.5% patients (15/24; first-line: 20% (3/15), second-line: 80% (12/15)). Overall, PSA response was reported in 66.7% (16/24) patients. The PSA response was 77.8% (7/9 patients) in the 2-weekly group and 60% (9/15 patients) in the 3-weekly group. The median decline in PSA was 96.31% in the 2-weekly group and 83.29% in the 3-weekly group; the median TTF was 6.7 and 6.5 months in the 2 weekly group and 3-weekly group, respectively. The median OS was 14.6 months (follow-up: 5.5–25.8 months) in the 2-weekly group whereas it was not reached in the 3-weekly group (follow-up: 7.9–15.6 months). The most common hematological AEs were anemia, lymphopenia, thrombocytopenia, and neutropenia whereas nausea, weakness, constipation, vomiting, and diarrhea were the most common (≥10%) nonhematological AEs. Overall, NDLS treatment was well tolerated without any new safety concerns. Conclusions. Nanosomal docetaxel lipid suspension (2-weekly or 3-weekly) was effective and well tolerated in patients with metastatic castration-resistant prostate cancer.


2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 198-198
Author(s):  
Tanya Burton ◽  
April H. Teitelbaum ◽  
Cat N. Bui ◽  
James Robert Spalding

198 Background: Prostate cancer is the most commonly diagnosed malignancy among men in the US; mortality rates are highest among those with castration-resistant prostate cancer (CRPC). Observational data on CRPC are limited. This study examined CRPC treatment patterns relative to NCCN guidelines in a large US health plan. Methods: This was a retrospective claims database analysis of commercial and Medicare Advantage enrollees with evidence of prostate cancer (ICD-9: 185.xx) between 07/01/06 – 03/31/11. CRPC patients were then identified based on prostate-specific antigen (PSA) progression (≥2 PSA increases based on ≥3 PSA values) and/or use of chemotherapy: docetaxel (DOC), mitoxantrone (MIT), estramustine (EST), or cabazitaxel (CAB). The CRPC index date was the first date of PSA progression or chemotherapy. Patients were continuously enrolled for 6 months before (baseline) and ≥6 months after the index date until 09/30/2011 or until death, if sooner (follow-up). Results: A total of 1651 patients met the CRPC selection criteria. Mean (SD) age was 70 ± 9 years, 1085 (66%) received DOC on the index date, and 467 (28%) died during follow-up. A third of patients with DOC received additional CRPC therapy during follow-up: 160 (15%) received MIT, EST, or CAB, and 239 (22%) received a secondary hormonal therapy (SHT: antiandrogens, aminoglutethimide, GnRH/LHRH antagonists, estrogen, or abiraterone acetate). Among 566 patients without DOC, 99 (17%) received a different chemotherapy (MIT = 45; EST = 52; CAB = 2), and 178 (31%) received a SHT. More than half 311 (55%) without DOC did not receive any other CRPC therapy during follow-up, of which 40 (13%) received bone-directed therapy (BDT: denosumab = 0; bisphosphonates = 27; radiation = 13). Conclusions: Consistent with NCCN guidelines, DOC was the most commonly used therapy. However, two-thirds of patients with DOC and over half of patients without DOC did not receive additional CRPC therapy after the index date. In addition, only 13% of patients with no CRPC therapy received any follow-up BDT. Additional research is warranted to understand whether clinical rationale, patient preference, or access to care may have resulted in patients not receiving additional therapy.


2021 ◽  
Vol 18 (3) ◽  
pp. 631-637
Author(s):  
Ke Yang ◽  
Tieqiu Li ◽  
Zhiyong Gao ◽  
Weiwei Zhang

Purpose: To investigate the influence of a combination of abiraterone and prednisone on serum chromogranin A (CgA) and neuron-specific enolase (NSE) in patients with metastatic castrationresistant prostate cancer (mCRPC) without previous chemotherapy, so as to provide reference data for drug therapy of prostate cancer. Methods: A total of 103 mCRPC patients without chemotherapy from January 2013 to March 2017 were included in this retrospective study. Seventy-one (71) patients received prednisone combined with abiraterone (study group), while 32 patients accepted prednisone (control group). The CgA, NSE and prostate-specific antigen (PSA) in the two groups were monitored, while PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS) were determined during follow-up. Results: PSA-PFS, rPFS and OS in the study group were significantly higher than those in the control group (p < 0.05). The increased proportion of CgA or NSE in the study group was significantly lower than that in the control group at 6 months of treatment (p < 0.05). The occurrences of NED before treatment and 6 months after treatment were both independent predictors of PSA and radiographic progression in the study group (p < 0.05). Conclusion: The combination of prednisone and abiraterone is helpful for prognosis in mCRPC patients that are not on chemotherapy. The occurrence of NED predicts mostly poor prognosis of mCRPC patients on a combination of abiraterone and prednisone


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